Determining catheter status

ABSTRACT

A method for determining the status of a catheter of an implanted infusion system, where the catheter is intended to deliver a fluid composition to CSF of a patient, includes monitoring catheter pressure, developing a pressure modulation profile based on the monitored pressure, and comparing the developed pressure modulation profile to a predetermined pressure profile. The predetermined pressure profile may be a profile of cerebrospinal fluid or a bolus infusion or withdrawal profile for the catheter. A determination of catheter status, such as properly functioning, occluded or leaky, can be made based on the comparison.

RELATED APPLICATIONS

This application is a continuation-in-part application of (i)application Ser. No. 11/731,356, filed on Mar. 30, 2007, which publishedon Oct. 2, 2008 as US 2008/0243074, and (ii) application Ser. No.11/778,400, filed on Jul. 16, 2007, which published on Jan. 10, 2008 asUS 2008/009837, which is a continuation of application Ser. No.10/836,115 filed on Apr. 30, 2004, now U.S. Pat. No. 7,320,676, whichclaims priority to U.S. Provisional Application No. 60/508,020, filed onOct. 2, 2003, which patents and applications are hereby incorporatedherein by reference in their respective entireties to the extent thatthey do not conflict with the present disclosure.

FIELD

The present disclosure relates generally to systems and methods foridentifying malfunctions in an implanted catheter of an infusion systemby sensing fluid pressure.

BACKGROUND

More than 100,000 individuals worldwide are implanted with an infusionsystem configured to deliver therapeutic agent to the cerebrospinalfluid (CSF) of a patient. Such systems typically have a reservoircontaining a supply of therapeutic substance awaiting delivery to thepatient's CSF. A pump may be fluidly coupled to the reservoir forcreating fluidic pressure to facilitate delivery of the therapeuticsubstance. A catheter provides a pathway for delivering the therapeuticsubstance to the CSF of the patient. All parts of the infusion systemneed to operate adequately to ensure proper delivery of therapeuticsubstances using the system.

While perhaps the least complex component of an infusion system,catheters can have operational problems or can develop operationalproblems. For example, catheters may be placed in the wrong locationwhen originally deployed or the catheters may move (migrate) over timesuch that fluids (e.g., therapeutic substances) delivered through thecatheters are not delivered to the originally intended delivery site(e.g., a CSF compartment).

Catheters can also become obstructed or clogged during use. A partial orcomplete blockage could prevent an adequate supply of the therapeuticsubstance from reaching the intended delivery site of the patient.

Catheters can also leak due to cuts, tears, etc. A leak, small or large,can also prevent some or all of the therapeutic substance from reachingthe selected internal delivery site of the patient and may result intherapeutic substance being delivered to unintended sites, which maycreate further issues.

Some infusion systems have been proposed which include pressure sensorscapable of monitoring pressure in the catheter to determine whether acatheter malfunction has occurred. However, to date, methods and systemsfor determining catheter status of the more than 100,000 alreadyimplanted infusion devices that deliver agents to a patient's CSF, wherethe methods and systems employ pressure sensors external to the deviceor patient, have been lacking.

SUMMARY

This disclosure, among other things, describes systems and methods thatallow for determination of catheter status in implanted medical systemsin which the catheter is intended to deliver therapeutic agent to atarget region of a patient, such as the CSF. The systems and methods, invarious embodiments, employ a probe that may be inserted percutaneouslyinto a patient to be placed in fluid communication with an implantedcatheter. The probe, such as a needle, has a lumen that can be fluidlycoupled with the catheter and a pressure sensor, which may be externalto the patient. Thus, the systems and methods described herein can beused to monitor the status of a catheter associated with in an implantedinfusion system that does not have an on-board pressure sensor.

In various embodiments, the methods and systems described herein takeadvantage of characteristic CSF pressure profiles that can betransmitted via the implanted catheter. As described herein, suchcharacteristic pressure profiles can be detected by an external pressuresensor operably coupled to a probe, such as a needle, having a lumen influid communication with the implanted catheter. A pressure profile maybe developed based on the pressure monitored via the external sensor,which can then be compared to a predetermined pressure profile for oneor more physiological parameters. For example, if the developed profileis indicative of a characteristic CSF pressure profile based onrespiration and heart rate is detected by the pressure sensor, thecatheter is likely to be properly positioned in the CSF and operatingproperly. If a characteristic CSF pressure profile is not detected bythe pressure sensor, there is likely a catheter malfunction, such as anocclusion, leak, or catheter migration.

In various embodiments, the methods and systems described herein takeadvantage of intracatheter pressure profiles generated by infusion offluid boluses through the catheter. Bolus infusions of fluid into acatheter result in characteristic pressure profiles in occludedcatheters, catheters that have leaks, and catheters that are free ofleaks and occlusions. These characteristic bolus profiles can bemeasured by the pressure sensor coupled to the probe in communicationwith the catheter. Accordingly, a bolus of fluid may be infused into thecatheter; e.g. via the infusion device, and pressure may be measured todetermine whether the pressure exhibits a characteristic bolus profileof an occluded catheter, a catheter having a leak, or a normallyfunctioning catheter. In some embodiments, fluid is withdrawn from thecatheter to monitor catheter status. Withdrawal of fluid from thecatheter can generate characteristic profiles similar to those generatedby bolus infusions.

In various embodiments, a system for determining the status of acatheter of an implanted infusion system includes a probe having a lumendefining an inner diameter. The inner diameter of the probe is 60% orless than 60% of the diameter of the catheter. The system also includesa tube operably coupled to the probe. The tube has a lumen defining aninner diameter. The inner diameter of the probe is 60% or less than 60%of the inner diameter of the tube. The system further includes apressure sensor operably coupled to the tube and configured to measurepressure in the lumen of the tube. Despite the difference in innerdiameter between the probe and the tube, the pressure sensor is capableof detecting a subtle change in pressure characteristic of a CSFpressure profile.

One or more embodiments of the methods or systems described hereinprovide one or more of benefits relative to existing methods or systemsfor monitoring or determining the status of an implanted catheter. Forexample, embodiments of the methods or systems described herein providea mechanism for determining catheter status in the over 100,000 patientsalready implanted with infusion systems configured to delivertherapeutic agents to cerebrospinal fluid of the patients. That is,proposals to include pressure sensors on board implantable infusiondevices are of little use for monitoring catheter status in patients whoalready have an infusion device without such technology implanted.Further, because embodiments of the methods and systems described hereinemploy a probe that can be percutaneously placed in fluid communicationwith an implanted catheter, catheter pressure can be monitored via theprobe external to the patient, which can provide several advantagesrelative to incorporating the pressure sensor in the implantableinfusion device. For example, the power requirements of the implantabledevice can be reduced if the device power source is not drained bymonitoring catheter pressure. Further processing power than may beemployed to run algorithms to determine whether the monitored pressureis indicative of a malfunction can be spared by performing themonitoring by an external device. These and other advantages will beapparent to those of skilled in the art upon reading the followingdetailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated into and form a partof the specification, illustrate several embodiments of the presentdisclosure and, together with the description, serve to explain theprinciples of the disclosure. The drawings are only for the purpose ofillustrating embodiments of the disclosure and are not to be construedas limiting the disclosure.

FIG. 1 is a schematic drawing of an embodiment of an implantableinfusion system

FIG. 2 is a schematic drawing depicting an embodiment of an implantedinfusion device.

FIG. 3 is a schematic drawing of an enlarged partial cross section of anembodiment of a catheter.

FIG. 4 is a schematic drawing of an embodiment of a pressure monitoringsystem and an embodiment of an implantable infusion system.

FIG. 5 is a schematic drawing of an enlarged partial cross section of anembodiment of a probe.

FIG. 6 is a schematic block drawing of an embodiment of a pressuremonitoring system operably coupled to a monitor for displaying apressure profile.

FIGS. 7-8 are schematic illustrations of embodiments of pressuremonitoring systems.

FIGS. 9-10 are schematic block drawings of embodiments of a pressuremonitoring systems.

FIG. 11A is a schematic drawing of a graph of infusion rate into acatheter over time.

FIG. 11B is a schematic drawing of graphs of intracatheter pressurefollowing the bolus infusion depicted in FIG. 11A. The curves correspondto an occluded (O), a leaky (L), and a normally functioning (N)catheter.

FIG. 12A is a schematic drawing of a graph of infusion rate into acatheter over time.

FIG. 12B is a schematic drawing of graphs of intracatheter pressurefollowing the infusion depicted in FIG. 12A. The curves correspond to aleaky (dashed lines), and a normally functioning (solid lines) catheter.

FIG. 12C is a schematic drawing of a graph of intracatheter pressurefollowing the infusion depicted in FIG. 12A. The curve corresponds to anoccluded catheter

FIG. 13 is a flow diagram providing an overview of an embodiment of amethod described herein.

FIG. 14 is a graph of fluid pressure (y-axis) versus time (x-axis) in acatheter having an infusion section located in the CSF in theintrathecal space.

FIG. 15 is a flow diagram providing an overview of an embodiment of amethod described herein.

FIG. 16 is a graph of cardiac activity (A), respiration activity (B) andfluid pressure in a catheter having an infusion section located in theCSF in the intrathecal space (C) versus time obtained from ananesthetized sheep on a ventilator.

FIG. 17 is a graph of cardiac activity (A), respiration activity (B) andfluid pressure in a catheter having an infusion section located in theCSF in the intrathecal space (C) versus time obtained from sheepsupported by a sling.

FIG. 18 is a graph of cardiac activity (A), respiration activity (B) andfluid pressure in a catheter having an infusion section located in theCSF in the intrathecal space (C) versus time obtained from a sheep. Thefluid pressure was obtained from a catheter access port of an infusiondevice coupled to the catheter external to the sheep.

FIG. 19 is a graph of fluid pressure in mmHg (y-axis) in cathetersversus time in seconds (x-axis) obtained (i) from a pressure sensoron-board an implantable infusion device, which on-board sensor wasconfigured to measure intracatheter pressure, and (ii) from a pressuresensor in communication with a catheter via a probe inserted into acatheter access port of an implantable infusion device. The pressure wasgenerated to mimic CSF fluid pressures measured in a sheep.

FIG. 20 is a graph of fluid pressure in mmHg (y-axis) in cathetersversus time in seconds (x-axis) obtained (i) from a pressure sensoron-board an implantable infusion device, which on-board sensor wasconfigured to measure intracatheter pressure, and (ii) from a pressuresensor in communication with a catheter via a probe inserted into acatheter access port of an implantable infusion device. The pressure wasgenerated to mimic CSF fluid pressures measured in a sheep.

FIG. 21 is a graph of fluid pressure (y-axis) versus time (x-axis) in acatheter having an infusion section located outside the CSF.

The schematic drawings presented herein are not necessarily to scale.Like numbers used in the figures refer to like components, steps and thelike. However, it will be understood that the use of a number to referto a component in a given figure is not intended to limit the componentin another figure labeled with the same number. In addition, the use ofdifferent numbers to refer to components is not intended to indicatethat the different numbered components cannot be the same or similar.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings that form a part hereof, and in which are shown byway of illustration several embodiments of devices, systems and methods.It is to be understood that other embodiments are contemplated and maybe made without departing from the scope or spirit of the presentdisclosure. The following detailed description, therefore, is not to betaken in a limiting sense.

All scientific and technical terms used herein have meanings commonlyused in the art unless otherwise specified. The definitions providedherein are to facilitate understanding of certain terms used frequentlyherein and are not meant to limit the scope of the present disclosure.

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” encompass embodiments having pluralreferents, unless the content clearly dictates otherwise.

As used in this specification and the appended claims, the term “or” isgenerally employed in its sense including “and/or” unless the contentclearly dictates otherwise.

As used herein, “have”, “having”, “include”, “including”, “comprise”,“comprising” or the like are used in their open ended sense, andgenerally mean “including, but not limited to.”

The present disclosure relates to, among other things, systems andmethods that allow for detection of catheter status in implanted medicalsystems in which the catheter is intended to deliver therapeutic agentto the CSF of a patient. The systems and methods can be used todetermine the status of a catheter implanted in a patient, where thecatheter is coupled to an infusion device that does not have an on-boardpressure sensor. Accordingly, the systems and methods described hereinprovide a way to monitor catheter status of infusion systems alreadyimplanted in more than 100,000 people.

The methods and pressure monitoring systems described herein may beemployed with any suitable implantable infusion system. FIGS. 1-2 showexamples of infusion systems 100 with which pressure monitoring systems300 and methods described herein may be used. The infusion systemdepicted in FIG. 1 includes an infusion device 110, a catheter 120, anda catheter access port 119 in fluid communication with the catheter 120.The infusion device 110 also includes a refill port 118 in communicationwith a reservoir for containing therapeutic agent (not shown) disposedwithin the housing of the device 110. The infusion device 110 mayinclude any suitable mechanism or structure capable of delivering one ormore fluids to a patient. The structures used to drive fluids in theinfusion devices may be powered (e.g., piston pumps, diaphragm pumps,peristaltic pumps, etc.), may be activated based on pressure to drivefluid out of a reservoir (e.g., using collapsing diaphragms, expandingbladders, etc.), or the like. Examples of some potentially suitable pumpassemblies may include, e.g., commercially available implantableinfusion pumps such as, for example, the SYNCHROMED II and EL pumps,manufactured by Medtronic, Inc., Minneapolis, Minn.

The infusion system 100 depicted in FIG. 2 is shown implanted in apatient. The infusion system 100 includes an infusion device 110 andcatheter 120 having a proximal end 122 attached to the infusion device110. The infusion device 110 may be surgically implanted in any suitablelocation, such as subcutaneously in the pectoral, abdominal or otherregion of the subject's body. The distal end 124 of the catheter 120 isimplanted in a patient such that the distal end 124 is located at theselected internal delivery site in the patient (in the intrathecal spaceof the patient as depicted in FIG. 2, the cerebroventricles, orelsewhere as desired). While not shown in FIG. 2, it will be understoodthat the depicted infusion device 100 may include a catheter access portin fluid communication with the catheter 120 as described above withregard to FIG. 1.

FIG. 3 depicts a portion of a catheter 120 in an enlargedcross-sectional view. The catheter 120 includes an elongated tubularportion 123 that preferably extends from the proximal end (not shown) tothe distal end 124. The catheter 120 depicted in FIG. 2 includes a lumen126 that terminates at opening 128 (or delivery region) at the distalend 124. Therapeutic substances (or other fluids) delivered from thepump assembly 110 to the catheter 120 pass through lumen 126 andpreferably exit the catheter 120 through opening 128.

The body of catheter 120 may be constructed of any suitable material,e.g., an elastomeric tube. Examples of some suitable materials include,but are not limited to, silicone rubber (e.g., polydimethyl siloxane) orpolyurethane, both of which can provide good mechanical properties andare very flexible. Suitable materials for the catheter 120 are alsopreferably chemically inert such that they will not interact withtherapeutic substances, body tissues, or body fluids while implanted inthe patient.

Where the catheter is to be used for intrathecal fluid delivery, it maybe preferred that at least a portion of the catheter 120 be sized to fitin the gap between the spinal cord and the dura within the intrathecalspace. Catheters intended for delivering fluids to other internaldelivery sites will be sized appropriately for those locations. Asanother consideration in sizing the catheter, the diameter of the lumen126 is preferably large enough to accommodate expected infusion rateswith acceptable flow resistance. The wall 121 of the catheter 120 ispreferably thick enough to withstand normal handling during the implantprocedure and forces from body tissues during normal motion. As anexample, a catheter intended for use in intrathecal fluid delivery mayhave an outside diameter of 1.25 millimeters (mm), an inside diameter of0.5 mm, and a wall thickness of 0.375 mm. Such a catheter may have alength of, e.g., 50 centimeters (cm) long to reach from, e.g., a druginfusion pump implanted in the patient's abdomen to the spine.

Although the opening 128 through which the fluid exits the catheter 120is depicted as a simple opening in the distal end 124 of catheter 120,such an opening 128 is only one embodiment of an infusion section thatmay be used in connection with the teachings presented herein. Otherembodiments of infusion sections may include, e.g., multiple openings,permeable membranes, or the like. Although the infusion section (opening128) of the depicted catheter 120 is located at the distal end 124 ofthe catheter 120, the infusion section(s) may be positioned at anylocation along the length of the catheter 120 that can be used todeliver the fluid to the selected internal delivery site.

Because physiological pressure modulations at the selected internaldelivery site are preferably transmitted into the fluid located withinthe lumens of catheters in various embodiments, the construction of theinfusion sections is preferably selected to provide for that pressuretransmission. In other words, the infusion sections are preferablycapable of transmitting physiological pressure modulations (e.g., fromthe CSF where the infusion sections may be located) into the fluidlocated within the catheter lumen.

Referring now to FIG. 4, a system for external monitoring intracatheterpressure to a patient is shown. In the depicted embodiment, a pressuremonitoring system 300 and an implantable infusion system 100 are shown.The pressure monitoring system includes a probe 310 that can be insertedtranscutaneouly into the catheter access port 119 of the infusion systemsuch that a lumen of the probe 310 is placed in communication with thecatheter 120. The probe 119 may contain an adaptor 315, such as aleur-type adaptor, to couple the probe to tube 320, having a lumen incommunication with a pressure sensor 330. While not shown, it will beunderstood that the pressure sensor 330 may be coupled to connector 315without intervening tubing 320 or may be integrated within probe 310,such as in the hub of a needle. In other words, the pressure sensor 330may be operably coupled to the probe 310 in any suitable manner. Thus,when the probe 310 is properly inserted into the port 119, pressurechanges in the catheter can be measured by the pressure sensor 330. Anysuitable pressure transducer or sensor 330 may be employed.

The pressure sensor 330 may be adapted or configured to read eithergauge or absolute pressure of the fluid in the lumen of the catheter120. Because the methods described below rely on comparison of pressuremodulation profiles, changes in ambient pressure may be of limitedimportance in implementing the methods because ambient pressure changescan typically be expected to exert the same influence on fluid in thecatheter lumen as it does at the selected internal delivery site (e.g.,on the CSF in the intrathecal space).

The probe 310 has an inner diameter d′ that, in some embodiments, isless than 60% of the inner diameter d of the catheter 120 and is lessthan 60% of the inner diameter d″ of the tube 320. Even with suchchanging inner diameters, pressure changes in the catheter indicative ofa CSF pressure profile are capable of being detected by the externalpressure sensor 330.

Tubing 320 may be of any suitable material, such as the materialsdescribed above with regard to the catheter. The tubing 320 may have anysuitable dimensions, such as an inner diameter of about 0.5 millimetersor greater. The tubing 320 may be of any suitable length, such as alength that allows a desired distance between the probe 310 and thepressure sensor 330.

Referring now to FIG. 5, an enlarged partial cross-sectional view of aprobe 310 is shown. The probe 310 includes an elongated tubular portion323 that preferably extends from the proximal end (not shown) to thedistal end 324. The probe 310 depicted in FIG. 4 includes a lumen 326that terminates at opening 328 at the distal end 324. Thus, when thedistal end 324 is inserted into a catheter access port, the lumen 326 ofthe probe 310 is placed in fluid communication with the catheter.

The body of probe 310 may be constructed of any suitable material, e.g.,rigid metallic material or a rigid plastic. The material should besufficiently stiff that is can be inserted transcutaneously into acatheter access port without compromising the integrity of the lumen.Examples of suitable materials include stainless steel and titanium. Invarious embodiments, the inner diameter of probe, as defined by thelumen 326, is less than 0.35 millimeters. In many embodiments, the probeis a 24-gauge or higher-gauge needle. For many catheter access ports ofimplantable infusion systems, needles of a gauge less than 24 gauge aretoo large of an outer diameter to be inserted into the port.

Referring now to FIG. 6 an external pressure monitoring system 300 mayinclude a monitor 400 for displaying pressure profiles. The pressureprofiles displayed may be pressure profiles developed from the pressuremeasured via pressure sensor 330, may be pressure profiles ofcharacteristic CSF pressure profiles or bolus profiles, which arediscussed in more detail below, or the like. The system may also includea processor that allows conversion of the measured pressure data intothe displayed pressure profile. A possessor may also be employed tocompare the developed pressure profiles to characteristic CSF or bolusprofiles to assist in determining whether the profiled developed fromthe measured pressures have characteristics indicative or not indicativeof a CSF or bolus profile.

The pressure monitoring system may also communicate with a second devicevia wires or wirelessly, such as via Bluetooth, USB, serial, or thelike, to transmit raw or processed pressure information to the seconddevice capable. The second device or a tertiary device operably coupledto the second device is capable of displaying the pressure information.The second device may be a physician programmer, patient programmer,computer, or the like.

Referring now to FIGS. 7-10, various alternative embodiments of pressuremonitoring systems 300 are shown. The systems 300 shown in FIGS. 7-8include a probe 310 fluidly coupled to tubing 320 via a connector 315 incommunication with a pressure sensor 330, e.g., as described above withregard to FIG. 4. The system further includes a tubing 322, which may bethe same or different than tubing 320. The tubing 322 is incommunication with a bolus delivery apparatus 350, capable of deliveringa bolus of infusate through probe 310 and into a catheter of animplantable infusion system when the probe is inserted into a catheteraccess port of an infusion device (see, e.g., FIG. 4). Pressure withinthe catheter may be measured via pressure sensor 330 following infusionof the bolus to determine whether pressure profiles characteristic of aproperly functioning catheter, a leaky catheter or an occluded catheteris produced, e.g. as described below in more detail.

In FIG. 7, the bolus delivery apparatus 350 includes a plunger 352 thatcan be manually depressed to deliver a bolus of fluid from the apparatus350 through the probe 310. The bolus delivery apparatus is operablycoupled to tubing 322 via a connector 317, which may be similar toconnector 315 as discussed above with regard to FIG. 4. The bolusdelivery apparatus 350 depicted in FIG. 8 includes an automated externalpump, such as a piston pump, a peristaltic pump, or the like, to delivercontrolled amounts of fluid in controlled amounts of time. One suitablepump than may be used is a Harvard pump.

The systems 300 depicted in FIGS. 7-8 include clamp 340 disposed abouttubing 320. The clamp 320 may be used in conjunction with the bolusdelivery apparatus 350 to withdraw a bolus of fluid from a catheter withwhich the probe 310 is in communication. The clamp may be located aboutthe tubing 320 at any suitable location. Generally, locating the clamp320 further from the probe 310 results in lower amounts of fluiddelivered. If the fluid delivered contains a therapeutic agent, it maybe desirable to minimize the incremental amount of therapeutic agentdelivered by positioning the clamp 320 away from the probe 330. Thebolus delivery apparatus 350, such as the syringe depicted in FIG. 7,may be activated to deliver or withdraw fluid, e.g. by pushing orpulling the plunger 352, until an appropriate reading is observed ordetected by pressure sensor 330, e.g. a pressure change of 1 psi or −1ppsi. A stop cock (not shown) or other mechanism may be used to closethe connection between the bolus delivery apparatus 350, the sensor 330and the tubing 320. It may be desirable to verify that the sensor 330still reads at the desired pressure, e.g. 1 psi or more above ambientpressure. The clamp 340 may then be quickly released, transferring thepressure or vacuum to the probe 310 and subsequently to the catheterfluid. The pressure decay back to baseline may be monitored via sensorto determine whether the catheter is properly functioning, e.g. asdescribed in more detail below. Of course, any other suitable method ormechanism for withdrawing a bolus of fluid may be employed.

For example and with reference to FIG. 9, an alternative embodiment of apressure monitoring system 300 capable of delivering or withdrawing abolus of fluid is shown. The depicted system 300 includes a first 350and second 351 pumps and first 360 and second 361 valves fluidly coupledto a lumen of the probe 310. The first pump 350 is configured to delivera bolus of fluid through the probe when optional valve 360 is open. Thesecond pump 351 is configured to withdraw fluid via the probe 310 whenoptional valve 361 is open. Use of such pumps 350, 351 can allow forprecise amounts of fluid to be delivered or withdrawn from the probe 310providing the ability to accurately determine whether a catheter, withwhich the probe is in fluid communication, has a leak or occlusion. Ofcourse other suitable configurations, such as a pump capable of pumpingfluid in both directions, may be used.

As shown in FIG. 10, a processor 500 may be used to control the pumps350/351, valves 360/361, or pressure sensor 330 to provide greaterprecision and accuracy of the system 300. The processor 500 may beoperably coupled to a monitor 400 for displaying monitored pressureprofiles, e.g. as discussed above with regard to FIG. 6.

As mentioned above, one way to determine the underlying cause of acatheter malfunction is to deliver or withdraw a bolus of fluid into orfrom the catheter and monitor the resulting pressure profile followingthe bolus. Any suitable bolus may be delivered over any suitable amountof time, provided that a characteristic profile can be measured. In someembodiments, e.g. where the implantable infusion device to which thecatheter is connected includes a programmable pump, the pump may beprogrammed to deliver a bolus of fluid and the resulting pressure andpressure decay profile may be observed via an appropriate pressuremonitoring system, such as the system depicted in FIG. 4. Alternatively,a system as depicted in, for example, FIGS. 7-10 may be employed todeliver or withdraw a bolus of fluid. In many cases, use of an externalsystem to deliver or withdraw the bolus may allow for greaterdisplacement of fluid, resulting in greater pressure changes that mayallow for more accurate evaluation of catheter status. Any suitablefluid, such as therapeutic fluid, water, saline, artificialcerebrospinal fluid, or the like may be delivered as the bolus.

Referring now to FIGS. 11A-B, schematic drawings showing hypotheticalplots of infusion rate versus time (A) and intracatheter pressure versustime (B) are shown. The time (x-axis) in FIGS. 11A and 11B aresimultaneous. As a bolus is delivered (FIG. 11A), pressure in a properlyfunctioning catheter transiently increases and returns to baselinefollowing a characteristic decay profile (see curve N). In an occludedcatheter (curve O), the pressure may (but does not necessarily) increasebeyond the maximum pressure observed in a normally functioning catheterfree from leaks an occlusions, and has a characteristically slower decayrate than a normal functioning catheter. In a catheter having a leak(curve L), the decay rate (time and profile, by which pressure returnsto baseline) is characteristically faster than in a properly functioningcatheter. It is notable that the differences in the profiles betweenoccluded, leaky, and properly functioning catheters are detectable incatheters that do not have flow restrictors or valves, which are lackingin most of the currently implanted catheters that are part of animplanted infusion system. The extent of the change in profile in anoccluded (O) or leaky (L) catheter relative to a properly functioningcatheter (N) will vary depending on the extent of the occlusion (e.g.,partial vs. full) or leak (e.g., small vs. large). Some partialocclusions or small leaks may not be readily detectable. However, suchleaks and occlusions may not be of therapeutic significance.

In addition, it will be understood that the differences in intercatheterpressure profiles between occluded (O), leaky (L), and properlyfunctioning (N) catheters will be amplified or attenuated depending onthe amount of fluid introduced into the catheter in the bolus, as wellas the rate the bolus is delivered to the catheter. Characteristicpressure profiles can be generated empirically, theoretically orotherwise for a given catheter of a given length with a given bolusdelivered at a given rate. The rates and bolus amounts can be varied toachieve a variety of profiles that may be used to determine whether theobserved profile in an implanted catheter is that of a properlyfunctioning catheter, an occluded catheter (possible increase in maximalpressure or slower decay rate) or of a leaky catheter (possible decreasein maximal pressure and faster decay rate).

Referring now to FIGS. 12A-C, schematic drawings showing hypotheticalplots of infusion rate versus time (A) and intercatheter pressure versustime (B,C) are shown. The time (x-axis) in FIGS. 12A-C are simultaneous.As shown in FIG. 12A, delivery of a bolus of fluid is followed bywithdrawal of a bolus of infusion (or vice-versa). Representativeresulting pressure profiles for a properly function catheter (solidlines) and a leaky catheter (dashed lines) are shown in FIG. 12B. Thepressure decay rate of a leaky catheter is expected to be faster thanthe decay rate of a non-leaky catheter. In FIG. 12C, a representativeresulting pressure profile of a fully occluded catheter is shown. Thepressure increases as fluid a bolus is infused into the blocked catheteruntil it reaches a maximum and returns to baseline upon withdrawal ofthe same amount of fluid that was introduced via the initial bolus.

The pressure profiles depicted in FIGS. 11-12 are shown for purposes ofillustration. It will be understood that the pressure profiles observedn practice may vary from those depicted. However, regardless of theprofile, the characteristics of a leaky, occluded, or properly functioncatheter may be detected and may be transmitted via a transcutaneouslyinserted probe in placed communication with the implanted catheter.

Referring now to FIG. 13 an overview of a method in accordance with oneembodiment of the disclosure is depicted. The method includes placing aprobe in communication with an implanted catheter (200), e.g. viainserting the probe into a catheter access port of an infusion device towhich the catheter is connected (see e.g. FIG. 4). A bolus of fluid maythen be delivered or withdrawn from the catheter via the probe (210).The bolus may be delivered by the implantable infusion device to whichthe catheter is connected or may be delivered via a pressure monitoringsystem, such as a system depicted in and described with regard to FIGS.7-10. The resulting intracatheter pressure may be monitored via anexternal pressure sensor to determine whether a pressure profilecharacteristic of a properly functioning catheter (220), an occludedcatheter (240), or a catheter having an unintended leak (260) isobserved or detected. If a pressure profile characteristic of a properlyfunctioning catheter is observed or detected (220), a determination thatno catheter malfunction exists can be made (230). If a pressure profilecharacteristic of an occluded catheter (240) or a leaky catheter (260)is observed or detected, a determination that a catheter malfunctionexists can be made (250). If the results are inconclusive, the processor a portion thereof may be repeated.

As mentioned above, another way to determine the status of a catheter ofan implantable infusion device is to monitor intracatheter pressure forcharacteristic physiologic pressure changes of cerebral spinal fluid(CSF) in which the catheter is implanted. Examples of such methods aredescribed in U.S. Patent Application Publication No. 2008/0243074A1,entitled CATHETER MALFUNCTION DETERMINATIONS USING PHYSIOLOGIC PRESSURE,published on Oct. 2, 2008, which patent application is herebyincorporated herein by reference in its entirety to the extent that itdoes not conflict with the present disclosure.

An example of a representative pressure profile of CSF in an animal,such as a sheep or dog, on mechanical ventilation is shown in FIG. 14.Pressure in the CSF has characteristic patterns that can be transmittedto a catheter in communication with the CSF, and thus through a probeand to an external pressure sensor. The data plotted in FIG. 14demonstrates these patterns, where the plot 20 represents pressure offluid within a lumen of a catheter located in fluid communication withthe CSF. The pressure profile includes repeating major peaks 22representative of patient respiration activity and repeating minor peaks24 representative of cardiac activity (i.e., heartbeats). The majorpeaks 22 and minor peaks 24 are transmitted into the fluid in the lumenfrom the CSF (into which the lumen opens). The major peaks 22 repeatabout every 2 to 10 seconds, which corresponds to about 30 to 6 breathsper minute. Typically, major peaks 22 repeat about every 3 to 5 seconds,which corresponds to about 20 to 12 breaths per minute. The amplitude ofthe major peaks 22 can vary (e.g., depending on the nature of thecatheter), but are often less than 4 mmHg in amplitude, typicallybetween about 1 mmHg and about 4 mmHg or between about 1 mmHg and 3 mmHgwithin a catheter such as Medtronic, Inc.'s Model 8709SC or 8731SCsilicone catheters with an inner diameter of about 0.53 mm.

The minor peaks 24 repeat about every half second to about every secondand a half, which corresponds to about 40 to 120 heart beats per minute.Typically, the minor peaks 24 repeat about every 0.6 seconds to aboutevery 1 second, corresponding to a heart rate of about 100 beats perminute to about 60 beats per minute. The amplitude of the minor peaks 24can vary (e.g., depending on the nature of the catheter), but are oftenbetween about 0.5 mmHg and about 1 mmHg in amplitude within a cathetersuch as Medtronic, Inc.'s Model 8709SC or 8731SC silicone catheters withan inner diameter of about 0.53 mm.

It should be noted that the pressure associated with respiration isexaggerated in cases where an animal is on mechanical ventilation (see.e.g, FIGS. 14, 16 and 18) relative to the free-breathing animal.Accordingly, the differences in amplitude of the peaks corresponding torespiration (major peaks) and heart rate (minor peaks) may not be asdiscernable in a free-breathing animal or human. It will be understoodpressure changes that generally repeat in coordination with the animal'sor patient's breathing or heart rate may be detected, regardless of theamplitude. In some instances, it may be difficult to detect pressurechanges associated with both breathing and heart rate. However, pressurechanges in the CSF or other fluid filled compartment associated with oneor the other of heart rate and respiration are typically detectable andare transmittable via a catheter having an infusion section opening intothe compartment. In some embodiments, characteristic pressure changesassociated with one or both of heart rate and respiration are detectedto determine catheter status.

Although physiological pressure modulations may be caused by respirationand/or cardiac activity at the selected internal delivery site, otherphysiological pressure modulations may be caused by, e.g., changes inposture. For example, as a patient moves from a horizontal (e.g.,supine, prone, etc.) position to an upright position, the spinal columnof a human moves from a generally horizontal orientation to a generallyvertical orientation. In response to such posture changes, the fluidhead of the CSF within the intrathecal space will change. Fluid-headpressure modulations caused by posture changes will typically be greatertowards the lower end of the spinal column due to the larger volume ofCSF located above the lower end of the spinal column when the spinalcolumn is generally vertical. Such physiological pressure modulationsmay be controlled by directing a patient to change posture andmeasuring/detecting the resulting pressure modulations.

Other physiologic parameters that can result in a CSF pressure changethat can be detected via a pressure monitoring system as describedherein include pressure changes due to a patient coughing or performinga valsalva maneuver (forceable exhalation against a closed airway thatcan be done by closing one's mouth and pinching one's nose shut).

The method depicted in FIG. 15 may be carried out using an externalpressure sensor operably coupled to a probe that can placed incommunication with an implanted catheter, e.g. via a port, such as acatheter access port, in fluid communication with the catheter. Themethod includes placing the probe in communication with the catheter(200) and measuring pressure via the pressure sensor operably coupled tothe probe (210). A pressure profile may be developed based on themeasured pressure and a determination can be made as to whether thepressure profile is characteristic of a CSF pressure profile (e.g., asshown in, and discussed with regard to, FIG. 14, as produced by aposture change, a cough, a valsalva maneuver, or the like). If thedeveloped profile based on the measured pressure is characteristic of aCSF pressure profile, a determination may be made that the catheter isfunctioning properly (230).

While much of the description provided above related to monitoringpressure changes in the CSF due to physiologic parameters, it will beunderstood that many similar pressure changes can be observed in otherfluid filled compartments of a patient, such as a patient's vasculature.Accordingly, the teachings present herein may be readily applied tomonitoring intracatheter pressure changes due to physiologicalparameters, where the catheter has an opening in the patient's vascularsystem. Determinations as to whether an occlusion or leak exists in acatheter having a delivery region implanted in a patient's artery, veinor the like may be performed in a manner similar to that described abovewith regard to a catheter having a delivery region implanted in the CSF.

Further, it will be understood that the bolus pressure profiles asdescribed herein (e.g., as described with regard to FIGS. 11-13) can beeffectively monitored regardless of where the catheter is intended todeliver fluid. That is, such bolus pressure profiles can be detected incatheters having a delivery region implanted in the patient's CSF,vasculature, solid tissue, or at any other location in the patient.

Whether a characteristic pressure profile following delivery orwithdrawal of a bolus or associated with a physiological parameter isused to determine the status of an implanted catheter, characteristicpressure patterns, shapes, or profiles may be used to identify cathetermalfunctions. Pressure modulation profiles may be developed based onmonitored pressure and compared to predetermined pressure profiles, suchas predetermined intracatheter bolus pressure profiles or predeterminedphysiologic profiles, for determining the status of the catheter.Predetermined pressure profiles may be generated based on empiricalmeasurements within an individual, a group of individuals orpopulations. The predetermined profiles may be averaged within orbetween individuals or groups. The predetermined profiles may begenerated based on pressure measured within a fluid filled compartment,such as the CSF, within a catheter opening into the fluid filledcompartment, or the like. In some embodiments, predetermined pressureprofiles are generated, at least in part, on theoretical considerations.For example, a pattern with rising and falling pressures repeating everytwo to ten seconds in conjunction with a patient's breathing pattern canbe considered a predetermined pressure profile correlating torespiration without any empirical data. Predetermined pressure profilesfor bolus delivery and withdrawal may likewise be determined based onknown compliance and resistance of a given catheter or catheter type, byempirical test within a patient or sample of patients, by bench testcharacterization, or by purely theoretical considerations. The pressuremeasurements in FIGS. 11, 12 and 14 depict pressure measurements as afunction of time to illustrate the principles described herein. Itshould be understood that these pressure curves are presented asnon-limiting examples. Although scales may be included, the systems andmethods described herein are not limited to catheters in which thesesame pressures are developed. Rather, the profiles, shapes or patternsof the pressure curves may be used to identify catheter malfunctions inconnection with the methods and systems presented herein.

Depending on the characteristic pressure profile monitored, the methodsdescribed herein may involve a variety of different analyses. Potentialanalytical methods may include, e.g., direct observation of the pressuremodulation profile (e.g., on a display), comparison of the pressuremodulation profile to a selected pressure profile (using, e.g., alook-up table, etc.), etc. In some methods, the physiological eventsthat impact the pressure modulation profile may be tracked andcorrelated to changes in the pressure modulation profile (e.g., heartrate may be monitored, respiration may be monitored (using, e.g.,thoracic impedance, etc.). In some embodiments, analytical methods tomeasure, for example, p-p amplitude in frequency band of interest may beused.

If it is determined that a catheter malfunction exists, a variety ofactions may be taken. For example, the delivery of fluid through thecatheter may be terminated; the rate of delivery of the fluid may bechanged, etc.

While most of the discussion presented above was with regard todetermining the status of a catheter in an implantable infusion system,it will be understood that the teachings presented herein may be readilyapplied to other systems employing implanted catheters. By way ofexample, the status of a catheter of a shunt system may be monitored viaan external pressure sensor in accordance with the teachings presentedherein. Many shunt systems include a catheter positioned in a cerebralventricle with a port implanted in or near the skull. The port is influid communication with the catheter, and thus with the CSF of theventricle. A probe can transcutaneously access the port, and a pressuresensor coupled to the port can be used to monitor intracatheterpressure, e.g. as described above with regard to an implantable infusionsystem, to determine whether the catheter is properly functioning oroccluded.

In the following, non-limiting Examples are provided of systems andmethods for monitoring intracatheter pressure via a pressure sensoroperably coupled to a probe transcutaneously placed in fluidcommunication with an implanted catheter.

EXAMPLES Example 1 Monitoring of Intracatheter Pressure of a CatheterImplanted in a Sheep Via an External Monitoring System

A sheep was anesthetized and a Medtronic, Inc. Model 8709 one-pieceintrathecal catheter was introduced into the intrathecal space via alumbar puncture and advanced to T6 under fluoroscopic monitoring. Theextraspinal portion of the catheter was tunneled subcutaneously tobetween the shoulder blades and externalized through stab incisions. Thecatheter was anchored securely to the skin after closure of the surgicalincision. A twenty three gauge needle was attached to the externalizedcatheter to provide a connection to a pressure transducer (HospiraTransPac IV, Hospira, Inc). Transducer signals were conditioned throughBioPac DA 100 C amplifiers (Biopac Systems, Inc.) with the gain set to5000, bandwidth of 300 Hz, at a 16-bit sample rate of 200 Hz.Intrathecal pressure, via the catheter, ECG, and respiration activitywere monitored. FIGS. 16-17 show plots of cardiac activity (A, ECG),respiration activity (B), and intrathecal pressure (C) in theanesthetized sheep on a ventilator (FIG. 16) and the same sheep awakeand supported by a sling (FIG. 17). As shown in the data plotted inFIGS. 16-17, the intrathecal catheter pressure profile is a composite ofthe respiration activity (respiration rate) and cardiac activity (heartrate).

Referring now to FIG. 18, a plot of ECG activity, respiratory activityand intrathecal pressure in the same sheep as described with regardFIGS. 16-17 above is shown. The data presented in FIG. 18 regarding theintrathecal pressure were obtained from a catheter access port of aSynchroMed II infusion device (Medtronic, Inc.) coupled to theexternalized catheter, while the sheep was under anesthesia and on aventilator. To obtain the pressure signal, a 24 gauge Huber needleconnected to a pressure transducer via a short length of fluid filledtubing was inserted into the catheter access port. As in FIGS. 16-17,the intrathecal pressure profile (C) depicted in FIG. 18 reflects acomposite of respiration activity (B) and cardiac activity (A), withmajor peaks corresponding to respiration rate and minor peakscorresponding to heart rate. While the pressure waveforms in FIG. 18 arediscernable, they are attenuated or dampened relative to those shown inFIGS. 16-17. Nonetheless, the data presented in FIG. 18 shows that it ispossible to monitor the pressure in a catheter that opens intocerebrospinal fluid space via a catheter access port of an implantablemedical device.

Example 2 Monitoring of Intracatheter Pressure of a Catheter in anArtificial System Via an External Monitoring System

Referring now to FIGS. 19-20, plots are shown of pressure measured via(i) a pressure transducer in communication with a catheter andincorporated into an implantable medical device and (ii) a pressuretransducer in communication with a catheter via a catheter access portof a SynchroMed II infusion device (Medtronic, Inc.). A 24-gauge needlewas inserted into the catheter access port and coupled to the pressuretransducer via a short length of fluid filled tubing. In both cases, thecatheters were placed in fluid communication with an artificial sourcedesigned to reproduce CSF pressure recorded in resting sheep (FIG. 19)and sheep on a treadmill (FIG. 20). The pressure traces measured by boththe pressure transducer incorporated into the infusion device and thepressure transducer coupled to the needle inserted in the catheteraccess port are shown in both FIG. 19 and FIG. 20. Because the measuredpressure profiles are nearly identical, it is difficult to discern thedifference between the two traces. The data presented in FIGS. 19-20illustrate that catheter pressure can be monitored via an externalpressure transducer in communication with the catheter via a needleinserted into a port in communication with the catheter (the catheteraccess port of a SynchroMed II infusion device) as well as pressure canbe monitored via a pressure sensor on-board an implantable infusiondevice.

Example 3 Monitoring of Intracatheter Pressure Via an ExternalMonitoring System, where the Catheter is Positioned Outside the CSF

For purposes of comparison and with reference to FIG. 21, a plotdemonstrating the pressure recorded within the fluid of a lumen of acatheter when the opening (e.g., infusion section) of the lumen islocated outside of the intrathecal space is shown. As seen in plot 30 ofFIG. 21, the pressure profile of the fluid located within the lumen whenthe opening is located outside of the intrathecal space is notnoticeably modulated by physiological activity (such as, e.g.,respiration or cardiac activity). It is theorized that the interstitialfluid pressure, i.e., the fluid pressure within the body but outside ofany enclosed system (e.g. fluid-filled space (such as a blood vessel,intrathecal space, etc.), in an organ, etc.) is relatively constantthroughout the body. When a catheter lumen opens within thisinterstitial space, significant pressure modulations are not typicallyobserved in the lumen, with the resulting pressure modulation profileappearing similar to that depicted in FIG. 21. Pressure modulationprofiles for catheters that are blocked or are leaking within theinterstitial space will also not typically include modulationsindicative of physiological pressure modulations. It should be notedthat if the catheter has a leak at a location within the CSF, acharacteristic CSF pressure profile may be detected with in thecatheter, but the catheter may be delivering therapeutic agent to anundesired location within the CSF.

Those skilled in the art will recognize that the preferred embodimentsmay be altered or amended without departing from the true spirit andscope of the disclosure, as defined in the accompanying claims.

What is claimed is:
 1. A method for determining status of a catheter ofan implanted infusion system, wherein the infusion system includes animplantable infusion device operably coupled to the catheter, thecatheter having a delivery region intended to be positioned in a targetlocation of a patient, the delivery region being in communication with alumen of the catheter, the implantable infusion device (i) configured tocause an agent stored in a reservoir to be delivered via the deliveryregion of the catheter through the lumen of the catheter, and (ii)having a port in communication with the lumen of the catheter, themethod comprising: percutaneously inserting a distal end of a probe intothe port, the probe having a lumen, wherein the lumen of the probe is incommunication with the catheter when the distal end of the probe isinserted into the port, and wherein the lumen of the probe is incommunication with a pressure sensor; measuring pressure via thepressure sensor; developing a pressure modulation profile based on themeasured pressure; and comparing the developed pressure modulationprofile to a predetermined pressure profile of the target location. 2.The method of claim 1, wherein the target location is the cerebrospinalfluid, and wherein the predetermined pressure profile comprises one ormore of (i) a peak corresponding to the patient's respiratory activityand (ii) peaks corresponding to the patient's cardiac activity.
 3. Themethod of claim 2, wherein the predetermined pressure profile comprisesa plurality of peaks that repeat every two to ten seconds, correspondingto the patient's respiratory rate, and a plurality of peaks that repeatevery half second to second a half, corresponding to the patient'scardiac activity.
 4. The method of claim 1, further comprisingdetermining whether a catheter complication exists based on thecomparison between the developed pressure modulation profile to thepredetermined pressure profile of cerebrospinal fluid.
 5. The method ofclaim 4, wherein a catheter complication is determined to exist if thedeveloped pressure modulation profile does not exhibit a predeterminedcharacteristic of the predetermined pressure profile.
 6. The method ofclaim 1, wherein the predetermined pressure profile comprises aplurality of peaks that repeat every two to ten seconds, correspondingto the patient's respiratory activity.
 7. The method of claim 1, whereinthe predetermined pressure profile comprises a plurality of peaks thatrepeat every half second to second and a half, corresponding to thepatient's cardiac activity.
 8. The method of claim 1, wherein thepredetermined pressure profile comprises a profile associated with acough or a valsalva maneuver.
 9. The method of claim 1, whereincomparison of the pressure modulation profile and the predeterminedpressure profile of cerebrospinal fluid is performed by a processor. 10.The method of claim 1, wherein the probe has an inner diameter definedby the lumen of the probe, wherein the catheter has an inner diameterdefined by the lumen of the catheter, and wherein the inner diameter ofthe probe is 60% or less than 60% of the inner diameter of the probe.11. The method of claim 1, wherein the probe is a 24 or higher gaugeneedle.
 12. The method of claim 1, wherein the target location isselected from the patient's cerebrospinal fluid and the patient'svasculature.
 13. A method for determining status of a catheter of animplanted infusion system, wherein the infusion system includes animplantable infusion device operably coupled to the catheter, thecatheter having a delivery region for delivering fluid to a targetlocation of a patient, the delivery region being in communication with alumen of the catheter, the implantable infusion device (i) configured tocause an agent stored in a reservoir to be delivered via the deliveryregion of the catheter through the lumen of the catheter, and (ii)having a port in communication with the lumen of the catheter, themethod comprising: percutaneously inserting a distal end of a probe intothe port, the probe having a lumen, wherein the lumen of the probe is incommunication with the catheter when the distal end of the probe isinserted into the port, and wherein the lumen of the probe is incommunication with a pressure sensor; infusing or withdrawing a bolus offluid into the lumen of the catheter; measuring pressure created by thebolus via the pressure sensor; developing a bolus pressure modulationprofile based on the measured bolus pressure; and comparing thedeveloped bolus pressure modulation profile to a predetermined boluspressure profile.
 14. The method of claim 13, further comprisingdetermining whether the catheter is occluded or has a leak based on thecomparison of the developed bolus pressure modulation profile to thepredetermined bolus pressure profile.
 15. The method of claim 14,wherein the catheter is determined to be occluded if developed boluspressure modulation profile has a pressure decay rate slower than thepredetermined bolus pressure profile.
 16. The method of claim 14,wherein the catheter is determined to have a leak if developed boluspressure modulation profile has a pressure decay rate faster than thepredetermined bolus pressure profile.
 17. The method of claim 13,wherein comparison of the pressure modulation profile and thepredetermined pressure profile of cerebrospinal fluid is performed by aprocessor.
 18. The method of claim 13, wherein infusing or withdrawing abolus of fluid into the lumen of the catheter comprises infusing a bolusof fluid into the lumen of the catheter.
 19. The method of claim 13,wherein infusing or withdrawing a bolus of fluid into the lumen of thecatheter comprises withdrawing a bolus of fluid from the lumen of thecatheter.
 20. The method of claim 13, wherein the probe has an innerdiameter defined by the lumen of the probe, wherein the catheter has aninner diameter defined by the lumen of the catheter, and wherein theinner diameter of the probe is 60% or less than 60% of the innerdiameter of the probe.